According to Vink, Exp. Op. Invest. Drugs, October 2002, 11(1) 1375-86, and Vink, Exp. Op. Invest. Drugs, (2004) 13(10) 1263-74, “traumatic brain injury (TBI) is one of the leading causes of death and disability in the industrialized world and remains a major health problem with serious socioeconomic consequences. In industrialized countries, the mean incidence of traumatic brain injury (TBI) that results in a hospital presentation is 250 per 100,000. In Europe and North America alone, this translates to more than 2 million TBI presentations annually. Approximately 25% of these presentations are admitted for hospitalization. Those individuals who survive TBI are often left with permanent neurological deficits, which adversely affect the quality of life and as a result, the social and economic cost of TBI is substantial. Despite the significance of these figures, there is no single interventional pharmacotherapy that has shown efficacy in the treatment of clinical TBI.”
It is well known that TBI causes edema in the brain, thereby elevating intrancranial pressure (ICP). Unterberg, Neuroscience, 129, 2004, 1021-1029. According to Bhardwaj, Stroke, 2000, 31, 1694-1701, intravenous administration of osmotic agents susch as mannitol and hypertonic saline have potent anti-edema action, presumably by drawing water from interstitial and intracellular spaces into the intravascular compartment. However, the use of such agents remains controversial. For example, the long term beneficial effects of mannitol remain unknown. There is some evidence that repeated doses of mannitol may even aggravate brain edema. Lastly, mannitol fails to be effective in some patients, even after repeated doses. Schwarz, Stroke, 2002, 33, 136-140.